Abstract
We developed a novel carbon nanoparticle-Fe (II) complex prepared via suspension injection (CNSI-Fe) to induce cancer cell ferroptosis through direct intratumoral delivery of ferrous iron. Preclinical studies have demonstrated that CNSI-Fe has promising antitumour effects, thereby prompting this first-in-human, single-arm, open-label, dose-escalation phase I trial in patients with refractory solid tumors. Primary objectives included assessments of safety and tolerability and the determination of dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Secondary objectives included the determination of preliminary antitumour efficacy and pharmacokinetics. Applying a 3 + 3 design across five doses (30-150 mg), a total of 19 enrolled patients received CNSI-Fe treatment. The MTD was not reached, and only one patient (in the 90 mg cohort) experienced DLT events. For all treated patients (n = 19), the common adverse events included injection site pain (89.5%), hypertension (52.6%), elevated serum iron levels (47.4%), and anemia (47.4%). Pharmacokinetic analysis revealed rapid iron absorption (peak time: 0.15-0.41 h) and clearance (half-life: 1.96-5.06 h), with peak serum concentrations ranging from 3520.33 to 13961.67 ng/mL. Preliminary efficacy estimates revealed an overall response rate of 10.5% and a disease control rate (DCR) of 84.2%. Notably, the DCR reached 100% in patients with lymph node and sarcoma lesions. Overall, CNSI-Fe demonstrated a favorable safety profile and promising antitumour activity (ClinicalTrials.gov identifier: NCT06048367), supporting further investigations in a phase II trial.